Influenza, commonly known as the flu, is an infectious disease of birds and mammals caused by an RNA virus of the family Orthomyxoviridae (the influenza viruses). In humans, common symptoms of influenza infection are fever, sore throat, muscle pains, severe headache, coughing, weakness, and fatigue. (Merck Manual Home Edition. Influenza: Viral Infections). In more serious cases, influenza causes pneumonia, which can be fatal, particularly in young children and the elderly. Sometimes confused with the common cold, influenza is a much more severe disease and is caused by a different type of virus. Eccles, R (2005). “Understanding the symptoms of the common cold and influenza”. Lancet Infect Dis 5 (11): 718-25. Although nausea and vomiting can be produced, especially in children, (Merck Manual Home Edition. Influenza: Viral Infections) these symptoms are more characteristic of the unrelated gastroenteritis, which is sometimes called “stomach flu” or “24-hour flu”. Seasonal Flu vs. Stomach Flu by Kristina Duda, R.N.; accessed Mar. 12, 2007 (Website: “About, Inc., A part of The New York Times Company”).
Flu spreads around the world in seasonal epidemics, killing millions of people in pandemic years and hundreds of thousands in non-pandemic years. Three influenza pandemics occurred in the 20th century and killed tens of millions of people, with each of these pandemics being caused by the appearance of a new strain of the virus in humans. Often, these new strains result from the spread of an existing flu virus to humans from other animal species. Since it first killed humans in Asia in the 1990s, a deadly avian strain of H5N1 has posed the greatest risk for a new influenza pandemic.
Vaccinations against influenza are most commonly given to high-risk humans in industrialized countries (WHO position paper: influenza vaccines WHO weekly Epidemiological Record 19 Aug. 2005, vol. 80, 33, pp. 277-288), and to farmed poultry (Villegas, P (1998). “Viral diseases of the respiratory system”. Poult Sci 77 (8): 1143-5. PMID 9706079). The most common human vaccine is the trivalent flu vaccine that contains purified and inactivated material from three viral strains. Typically this vaccine includes antigenic material from two influenza A virus subtypes and one influenza B virus strain and is given by intramuscular injection. A vaccine formulated for one year may be ineffective in the following year; the influenza virus changes rapidly over time and hence annually different strains become dominant.
Another vaccine, live attenuated, cold-adapted influenza vaccine (LACAIV) is becoming widely recognized as a better alternative to conventional vaccines, especially in children ages 1-5 years old. One clear advantage is that this vaccine can be administered via a nasal spray into the upper respiratory tract as opposed to intramuscular injection. Further, LACAIV has theoretical advantages over intramuscular influenza shots in that it induces sIgA antibody which prevents flu infection of the upper respiratory tract (Renegar, Kathryn B. and Small, Parker A., Jr., Immunoglobulin A mediation of murine nasal anti-influenza virus immunity. J. of Virology, 65:2146-2148, 1991), cell mediated immunity which enhances recovery (Bender, B. S. Coroghan, T., Liping, Z and Small, P. A. Jr., Transgenic mice lacking major histocompatibility complex-restricted class 1 T-cells have delayed viral clearance and increased mortality following influenza virus challenge, J. Exp. Med. 175:1143-1145, 1992), and serum IgG antibody which has long been known to prevent infection of the lungs (viral pneumonia) (Loosli, C. G., D Hamre, and B. D. Berlin, Airborne influenza virus A infection in immunized animals, Trans. Ass. Amer. Physicians 66:222-230,1953), but not to prevent infection of the upper respiratory tract (Ramphal, R. Cogliano, R. C. Shands, J. W., Jr. and Small, P. A., Jr., Serum antibody prevents murine influenza pneumonia but not influenza tracheitis, Infect. Immun. 25:992997, 1979). These theoretical advantages of LACAIV, however, are not always observed in field trials. In fact, it has been shown that in individuals age 18 to 46 years old, LACAIV is significantly less effective than intramuscular injection of an inactivated vaccine. (Ohmit et al., Prevention of Antigenically Drifted Influenza by Inactivated and Live Attenuated Vaccines, N Engl J Med, 355:2513-2522, 2006). This problem is perplexing and casts a shadow over the use of LACAIV as a viable vaccine alternative for adults.